El-Sharkawi Fathia, El Sabah Mahmoud, Hassan Zeinab, Khaled Hussein
Department of Biochemistry and Molecular Biology, Faculty of Pharmacy, Helwan University, Cairo, Ein helwan, Egypt.
J Biomed Sci. 2014 Aug 19;21(1):72. doi: 10.1186/s12929-014-0072-4.
Matrix metalloproteinases (MMPs) have long been associated with cancer-cell invasion and metastasis. Few studies are available that describe this association with bladder cancer either related or unrelated to schistosoma infection.Evaluating the urinary levels of MMP3 and MMP9 as diagnostic and prognostic biomarkers in different stages of schistosomal and non schistosomal bladder cancer was the aim of the present study.Urine samples were collected from 70 patients with schistosomal and non schistosomal bladder cancer at early and advanced stages and also from 12 healthy volunteers as controls. Urinary levels of MMP-3 and MMP-9 was measured by ELISA technique. Sensitivity and specificity of both markers were determined.
Urinary levels of both MMP-3 and MMP-9 were significantly elevated in all bladder cancer patients compared with controls. MMP-3 started to elevate in early stages of schistosomal bladder cancer ( 0.173 ng/ml) and non-schistosomal bladder cancer patients (0.308 ng/ml) compared to control (0.016 ng/ml) and remained elevated in advanced stages (0.166, 0.235 ng/ml) of both types of bladder cancer patients. In contrast, MMP-9 showed a significant elevation in advanced stages only of both schistosomal and non schistosomal bladder cancer patients (10.33, 21.22 ng/ml) compared to control (0.409 ng/ml) and this elevation of both markers was much higher in non schistosomal bladder cancer. Both Metalloproteinases were specific for the diagnosis of the disease but MMP-3 was more sensitive and this sensitivity was evident in the early stage (84.85% for MMP3, 27.28% for MMP9).
MMP3 may be the recommended urinary metalloproteinases as early diagnostic biomarker in the early stages of both types of bladder cancer although both MMP9 and MMP3 can be used in the diagnosis of advanced stages. Further studies are required on large number of urine samples to confirm these results.
基质金属蛋白酶（MMPs）长期以来一直与癌细胞的侵袭和转移有关。很少有研究描述这种与膀胱癌的关联，无论是否与血吸虫感染相关。本研究的目的是评估MMP3和MMP9的尿液水平作为血吸虫性和非血吸虫性膀胱癌不同阶段的诊断和预后生物标志物。收集了70例早期和晚期血吸虫性和非血吸虫性膀胱癌患者的尿液样本，并收集了12名健康志愿者的尿液样本作为对照。采用酶联免疫吸附测定（ELISA）技术测量尿液中MMP-3和MMP-9的水平。确定了两种标志物的敏感性和特异性。
与对照组相比，所有膀胱癌患者尿液中MMP-3和MMP-9的水平均显著升高。与对照组（0.016 ng/ml）相比，MMP-3在血吸虫性膀胱癌早期（0.173 ng/ml）和非血吸虫性膀胱癌患者早期（0.308 ng/ml）开始升高，并在两种类型膀胱癌患者的晚期（0.166、0.235 ng/ml）保持升高。相比之下，MMP-9仅在血吸虫性和非血吸虫性膀胱癌患者的晚期显著升高（10.33、21.22 ng/ml），而对照组为（0.409 ng/ml），并且这两种标志物在非血吸虫性膀胱癌中的升高幅度更高。两种金属蛋白酶对疾病的诊断具有特异性，但MMP-3更敏感，这种敏感性在早期阶段就很明显（MMP3为84.85%，MMP9为27.28%）。
MMP3可能是推荐的尿液金属蛋白酶，作为两种类型膀胱癌早期阶段的早期诊断生物标志物，尽管MMP9和MMP3均可用于晚期诊断。需要对大量尿液样本进行进一步研究以证实这些结果。
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